Erdheim-Chester disease: an unusual aetiology of bilateral lipomatous perinephric masses

Abstract

A 53-year-old man presented with a history of progressive abdominal distention for 1 year. Physical examination revealed large palpable masses in the bilateral flank regions. Contrast-enhanced CT of the abdomen showed bilateral, symmetrical large perinephric masses with fat attenuating areas, which was further confirmed on MRI. CT of the paranasal sinuses revealed circumscribed extraconal soft tissue mass in the left orbit, causing scalloping and erosion of the left orbital roof. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/CT showed FDG uptake in the bilateral perinephric masses. Based on imaging appearance, a diagnosis of Erdheim-Chester disease (ECD) was suggested. Ultrasound-guided biopsy from perinephric masses revealed a sheet of histiocytes with sprinkled lymphocytes and plasma cells in the background. The histiocytes were immunopositive for CD68, S100 and immunonegative for CD1a, which confirmed the diagnosis of ECD. The patient was started on interferon-α-2a and showed symptomatic improvement.

Background

Erdheim-Chester disease (ECD) is a rare variant of non-Langerhans cell histiocytosis with multisystem involvement. Skeletal system, cardiovascular system, central nervous system (CNS), pulmonary system and retroperitoneum are the common sites of involvement. The diagnosis is often challenging because of rarity of the disease and clinical manifestations similar to other systemic diseases. Radiology plays an important role to suggest the diagnosis. In this case report, unusual imaging features of ECD, such as large bilateral symmetric perirenal masses containing macroscopic fat and extraconal orbital mass causing scalloping and erosion of bone, are described on various cross-sectional modalities, highlighting their vital role in suggesting the diagnosis. To the best of our knowledge, only one case of ECD with macroscopic fat-containing masses is reported in the literature.¹

Case presentation

A 53-year-old man presented with complaints of progressive abdominal distention and pain for 1 year, and loss of appetite for 3 months. There was no history of weight loss and fever. There was no significant medical or family history. Physical examination revealed large, non-tender and firm-to-hard masses in bilateral flanks. Overlying skin was normal. General physical examination was within normal limits.

Investigations

Radiological investigations performed were contrast-enhanced CT (CECT) and MRI of the abdomen, and CT of the paranasal sinuses (PNS) and ultrasound-guided biopsy. CECT of the abdomen showed large, bilateral, symmetric, enhancing perinephric masses with renal sinus extension and causing compression of the renal parenchyma. The masses showed multiple, discrete fat attenuating areas (figure 1A, B). Contrast-enhanced MRI of the abdomen was also performed. The masses showed T2 intermediate to hyperintense signal intensity (figure 2A). Masses were hypointense on T1-weighted images with multiple straited T1 hyperintense areas within it, which suppressed on fat saturated (FS) sequences suggestive of (s/o) fat component (figure 2B, C). Diffusion restriction was seen on diffusion-weighted imaging sequences (figure 2D, E). Masses showed heterogenous postcontrast enhancement (figure 2F). The masses were encasing and splaying the renal vessels (figure 3A, B). Few nodular similar signal intensity soft tissue/lymph nodes were seen partly encasing the inferior vena cava (figure 2A). However, no soft tissue seen around the aorta. CT PNS revealed circumscribed, extraconal soft tissue mass in the left orbit in the superomedial part abutting the superior rectus muscle and causing scalloping and erosion of the left orbital roof (figure 4A, B). Osteosclerosis of the bilateral maxillary sinuses and ethmoid air cells were also seen (figure 4C). Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/CT was performed to look for multisystem involvement, which showed FDG uptake in the bilateral perinephric masses (figure 3C). Bones did not show increased uptake. Based on the imaging findings, possibility of ECD was considered. Histopathology of ultrasonography-guided biopsy specimen from the perinephric mass showed sheets of histiocytes with sprinkled lymphocytes and plasma cells in background (figure 5A, B). Touton giant cells were not seen. No emperipolesis and storiform fibrosis were noted. The histiocytes were immunopositive for S100, CD68 and immunonegative for CD1a (figure 5C, D). CD163, which is a more specific marker for histiocytes has not been performed in the current case due to unavailability. These findings were suggestive of a non-Langerhans cell histiocytosis; ECD.

Figure 1.

(A, B) CECT abdomen: Axial images of CECT abdomen showing bilateral, symmetrical mildly enhancing perinephric masses showing fat attenuating areas within (arrows) and causing mass effect on the renal parenchyma. CECT, contrast-enhanced CT.

Figure 2.

(A–F) Contrast-enhanced MRI abdomen: T2-weighted non-fat-saturated sequence axial image (A) shows T2 intermediate to hyperintense signal intensity mass in the bilateral perinephric space. T1 non-fat-saturated and fat-saturated axial images (B, C) show T1 hyperintense signal intensity areas which are hypointense on fat-suppressed images, suggestive of fat (arrows). ADC and DWI sequence axial image (D, E) show areas of hyperintensity on DWI (D) with hypointense signal intensity on ADC (E) suggestive of diffusion restriction. Postcontrast venous phase axial image (F) shows mild heterogeneous enhancement of mass. In addition, nodular soft tissue/lymph node seen around the inferior vena cava (arrow in figure A). ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging.

Figure 3.

(A, B) MRI abdomen and (C) ¹⁸F-FDG PET/CT. T2-weighted sequence axial image (A) shows the mass is encasing the bilateral renal vessels (arrows). Balanced turbo field echo sequence coronal image (B) shows perinephric mass causing renal parenchymal compression and extension into the renal sinus causing distortion of pelvicalyceal system (arrows). ¹⁸F-FDG PET/CT axial section (C) shows FDG uptake in the bilateral perinephric masses. ¹⁸F-FDG, fluorine-18 fluorodeoxyglucose; PET, positron emission tomography.

Figure 4.

(A–C) NCCT PNS. NCCT PNS coronal section in soft tissue window (A) shows circumscribed hypodense mass (arrow) in the extraconal compartment of the left orbit causing scalloping of the left orbital roof. Coronal sections in bone window (B, C) show erosion of the ethmoid air cells by mass (arrow) along with sclerosis of bilateral maxillary sinus and ethmoid air cells (arrow). NCCT, non-contrast CT; PNS, paranasal sinuses.

Figure 5.

(A, B) H&E stained and (C, D) immunohistochemistry section. H&E stained section (A) shows sheet of histiocytes with sprinkled lymphocytes and plasma cells in the background (100×), (B) sheets of histiocytes (400×) and immunohistochemistry (C, D) show that histiocytes are immunopositive for CD68 (200×) (C) and immunonegative for CD1a (100×) (D).

Differential diagnosis

Differential diagnosis based on imaging included liposarcoma and extramedullary haematopoiesis. Retroperitoneal liposarcoma demonstrates a variable amount of fat depending on the histological subtype. However, appearing as fat-containing masses, which are bilateral and symmetrically involving the perinephric regions, is a very rare presentation of liposarcoma; reported in literature in one case report.² Differentiating liposarcoma from the ECD (as seen in our case) is challenging on imaging; however, involvement of other sites, such as sclerotic bone lesions and orbital soft tissue masses helps in distinction.

Extramedullary haematopoiesis may present as perinephric soft tissue, which may show macroscopic fat tissue, without much mass effect on renal parenchyma.³ The possibility of extramedullary haematopoiesis was ruled out as investigations were negative for haemolytic, myeloproliferative and myelofibrotic disorders.

The histopathological differential diagnosis in this case are Rosai-Dorfman disease and IgG4 disease. We did not find emperipolesis in index case, which makes the Rosai-Dorfman disease less likely. The possibility of IgG4 was unlikely as plasma cells were not in abundance as well as the critical histopathological features of storiform pattern of fibrosis and obliterative phlebitis were not identified.

Treatment

The patient was started on interferon-α-2a (IFN-α) at a dose of 3 mIU three times a week.

Outcome and follow-up

On follow-up after 1 month and 3 months, there was symptomatic improvement in appetite and abdominal pain. Follow-up MRI is planned after 6 months.

Discussion

ECD is a rare systemic infiltrative non-Langerhans cell histiocytosis, classified under histiocytic and dendritic cell neoplasms in 2016 WHO classification of mature lymphoid, histiocytic and dendritic neoplasms.⁴ There is slight predilection for men and commonly seen in the fifth to seventh decade of life. The pathogenesis and aetiology of this disease is unknown. Some studies have suggested clonal neoplastic origin due to the presence of V600E BRAF mutations and other studies have proposed inflammatory origin due to raised levels of interleukins and IFN.^{5 6} Clinical presentation of ECD is variable due to variable involvement of different organs. This leads to diagnostic delay. The diagnosis is established on the basis of the radiological and histological findings.⁷

The commonly involved system is skeletal, seen in approximately 96% of cases and often presents as bone pain in 50% of cases.⁸ Extraskeletal sites of involvement reported are retroperitoneum (30%–50%), CNS, orbit, cardiovascular, lungs and skin.⁹ The index case had clinically presented with abdominal pain, distention and bilateral flank masses, which is an unusual presentation.

Infiltration by the foamy macrophages in the retroperitoneum presents radiologically as bilateral, symmetrical perinephric rind of soft tissue causing irregular contour of the kidney; described as hairy kidneys. Perinephric involvement is characteristic of the disease. Soft tissue coating around the aorta, which is commonly termed as coated aorta, is another manifestation. Other retroperitoneal structures can also be infiltrated, such as renal arteries, presenting as renovascular hypertension, and ureters, presenting as renal failure.¹⁰

In the index case, large bilateral symmetrical perinephric masses with involvement of renal sinus causing marked mass effect on the renal parenchyma and pelvicalyceal system was noted. Renal vessels were encased and stretched. Despite that, the patient did not have renal failure and renovascular hypertension. Renal parenchymal compression by the perinephric mass in ECD has been described in a case report and which required surgical resection to alleviate mass effect.¹¹

The striking feature in this case was presence of macroscopic fat in the bilateral perinephric masses. A case report described presence of macroscopic fat in the perinephric soft tissue in a patient with ECD.¹ It has been proposed that the cause of macroscopic fat in the perinephric mass is due to preexisting perirenal fat engulfed by aggregation of foamy histiocytes rather than lipid-laden macrophages itself. We agree with this theory, since MRI showed macroscopic areas of fat, which showed similar signal intensity characteristics as rest of the retroperitoneal fat. On in-phase and opposed phase imaging, chemical shift artefact between fat and soft tissue components were seen as well. In addition, rest of the soft tissue mass (even with presence of abundant foamy histiocytes) did not show any significant signal drop on opposed phase images.

Orbits are usually affected in bilaterally symmetric fashion, involving the intraconal and extraconal compartments, and present with exophthalmos. Sclerosis of the bone can also be seen, but erosion is rarely reported. Osteosclerosis of facial bones can also be seen in ECD.¹² In index case, osteosclerosis of the maxillary bones and ethmoid air cells were seen along with orbital extraconal mass causing bone erosion. The bone and orbital involvement was asymptomatic in our case. Other commonly affected systems, such as CNS, pulmonary and cardiovascular systems were not involved in the index case.

Systemic treatment is recommended in ECD, except if only one non-vital organ is involved causing no symptoms (such as bone). Medical management is recommended for symptomatic disease, asymptomatic CNS involvement and organ dysfunction. Treatment options include administration of corticosteroid, IFN-α and pegylated IFN-α (reported response rates from 50% to 80%), systemic chemotherapy, radiotherapy and targeted therapy such as BRAF and MEK inhibitors.¹³ Prognosis is variable, with worst outcome reported with CNS, pulmonary and retroperitoneal involvement.¹⁴ However, with diagnostic and therapeutic advancements, 5-year survival rates have improved over a period of time and approaches 83% in a recent study.¹⁴

In conclusion, large fat-containing perinephric masses and orbital mass causing scalloping are rare, but characteristic imaging manifestations of ECD. Radiology is an essential component of the diagnostic workup and characteristic imaging appearances direct towards the prompt diagnosis. Histopathology is recommended for confirmation.

Patient’s perspective.

My abdomen was increasing in girth associated with pain for 1 year. I was not feeling like eating anything. I consulted in surgical outpatient department and was advised a CT scan. I was told, it could be cancer and my entire family was devastated. After biopsy, I was told, it is a very rare disease. Treatment has been started and my appetite has improved.

Learning points.

• Bilateral, symmetrical large fat-containing perinephric masses are a rare imaging presentation of Erdheim-Chester disease (ECD).

• Liposarcoma and extramedullary haematopoiesis are the most common differential diagnosis and histopathological investigation is essential to confirm the diagnosis.

• It is important to consider ECD as a possible differential for bilateral, symmetrical fat-containing perinephric masses and to run immunohistochemistry for CD68 and CD1a.

• Skeletal system is commonly involved in ECD and sclerotic lesions are the hallmark.

• Medical management is recommended for symptomatic disease, asymptomatic central nervous system involvement and in cases with organ dysfunction.